EVALUATION OF CHEMOPREVENTIVE AGENTS IN DIFFERENT MECHANISTIC CLASSESUSING A RAT TRACHEAL EPITHELIAL-CELL CULTURE TRANSFORMATION ASSAY

The rat tracheal epithelial (RTE) cell focus inhibition assay was used to identify potential chemopreventive agents. Ninety-nine agents were evaluated for their ability to inhibit benzo[a]pyrene-induced transfo rmation of RTE cells. Freshly isolated RTE cells were exposed to benzo [a]pyrene alone or in combination with a chemopreventive agent. After 30 days in culture, transformed foci were scored and inhibition was qu antitated. in these studies, foci formation was inhibited mainly by ag ents which modulate the initiation of carcinogenesis by altering drug- metabolizing enzymes, inhibiting the binding of benzo[a]pyrene to DNA, enhancing detoxification of activated carcinogens, or by inducing epi thelial cell differentiation. Such agents include antioxidants, free r adical scavengers, glutathione S-transferase enhancers, vitamins, reti noids, and sulfhydryl compounds. Agents which inhibit ornithine decarb oxylase and arachidonic acid metabolism were not as effective. The RTE assay provides important data for agent selection prior to whole anim al-screening assays in the development of chemoprevention drugs.